Vitamin D is powerful stuff. The body usually produces its own, spurred on by sunlight. A century ago, people who couldn't get enough vitamin D—usually those living in northern latitudes where sunlight is scarce all winter long—risked developing rickets. Today, although many foods are fortified with vitamin D, Americans can find it surprisingly hard to get enough. For people working office jobs—or used to slathering on SPF 30 sunscreen to block the sun's rays—sunlight isn't always enough.

In recent years, researchers have linked low vitamin D levels to insulin resistance and diabetes. Overcoming insulin resistance, in particular, could be a way to head off type 2 diabetes before it sets in. "Right now, there's a lot of circumstantial evidence to suggest that giving people vitamin D might help with insulin resistance," says Preeti Kishore, MB, BS, an assistant professor at the Albert Einstein College of Medicine in New York.

But while circumstantial evidence might be good enough for a court of law, scientists want more—hard numbers that show one treatment is better than another. Kishore's research into vitamin D is funded by a grant to her mentor, Meredith Hawkins, MD, from the American Diabetes Association (supported by unrestricted funds from Merck). She is taking a close look at a type of cell called a macrophage.

Macrophages are specialized immune cells that attack invaders and, researchers now think, may have a secondary function as a cleanup crew. When fat cells get too large, they die, and macrophages move in to eliminate the dead tissue. That, Kishore says, may be why the cells are overrepresented in fatty tissue—and why inflammation, a sign that macrophages are at work, is often more severe in people who are overweight or obese.

For people with diabetes, the latest research suggests macrophage activity can have an added drawback. Macrophages at work produce chemicals called cytokines, some of which serve as signals to other parts of the body. "They can impair insulin action in the liver and muscle," Kishore says. "Higher cytokines means more insulin resistance," a key factor in type 2 diabetes.

Kishore is working to find a way to turn down the activity of macrophages in the body. After noticing that macrophages have special receptors for vitamin D, Kishore decided to look at whether vitamin D deficiency might be making macrophages more active—contributing to insulin resistance and inflammation in the process. "When you have less vitamin D, the macrophages are in a more active state," Kishore says. "We believe when you give people vitamin D, these inflammatory reactions will be reduced."

It was a research field that Hawkins was eager to encourage. "This is an incredibly important topic—there's been a lot of controversy," says Hawkins, a professor at the Albert Einstein College of Medicine and director of the Global Diabetes Initiative. "We really don't have evidence about the role of vitamin D deficiency in diabetes."Kishore started with a small group of people who had too little vitamin D in their bodies and were also insulin resistant (but did not have diabetes). After a brief initial screening for insulin resistance and vitamin D deficiency, participants in the study were hooked up with IVs in both arms that took blood samples every five minutes for six hours to assess insulin sensitivity.

The eight people in the study were then given large doses of vitamin D, 10 times as much as you might get from a daily multivitamin pill, every day for two months. At the end of the study, they were tested again for insulin resistance. The results were "pretty remarkable," Kishore says. "Two months of normal vitamin D levels improved hepatic insulin sensitivity"—the measure of the liver's responsiveness to insulin in the blood—"by 37 percent." On top of that, when small samples of fat tissue were removed and studied, Kishore found that macrophages were less active when vitamin D levels went up.

Hawkins is enthusiastic about her protégée's results. "The data from these studies indicate that for people with insulin resistance, vitamin D can make a big difference," she says. "This is a cheap, safe, effective solution that could make a real impact."

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